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Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

Primary Purpose

Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Laboratory Biomarker Analysis
Pharmacological Study
Vandetanib
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Neoplasm

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
  • Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy; patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; in addition, patients must be at least 3 weeks beyond the last session of radiation therapy; local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status should be less or equal to 3
  • Absolute neutrophil count more or equal to 750/mL
  • Platelets more or equal to 50,000/mL
  • Creatinine less or equal to 3 x upper limit of normal (ULN)
  • Total bilirubin less than or equal to 3.0
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support
  • Pregnant or lactating women
  • History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation
  • History of hypersensitivity to sirolimus, temsirolimus, everolimus
  • History of hypersensitivity to any component of the formulation
  • Patients unwilling or unable to sign informed consent document
  • Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia
  • History (within the last 3 months) or presence of stroke/cerebrovascular accident
  • Congenital long QT syndrome
  • Corrected QT for Fridericia (QTcF) interval greater than 500 ms that is not correctable to less than 500 ms such as with cessation of a causative medication, etc
  • History of myocardial infarction within 6 months with a residual arrhythmia that in the opinion of the investigator, increases the risk of ventricular arrhythmia
  • Presence of a symptomatic bradyarrhythmia or uncompensated heart failure

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vandetanib, everolimus)

Arm Description

Patients receive vandetanib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum tolerated dose
Will be defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%. Toxicity will be reported by type, frequency, and severity. Worst toxicity grades per patient will be tabulated for selected adverse events and laboratory measurements.
Anti-tumor efficacy of the combination in terms of response rate
The response rate will be estimated by dose level and tumor type, along with the exact 95% confidence interval. Efficacy will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria described in the supplement for response. Patients with lymphoma will be measured per the World Health Organization (WHO) criteria.
Maximum observed serum concentration (Cmax)
Will be estimated using standard non-compartmental methods
Pharmacodynamic (PD) parameters
PD biomarker concentration will be summarized by time points. The relationship between drug concentrations and PD effects will be explored graphically. Based on review of these graphs, analyses to describe the relationship may also be performed.
Observed trough serum concentration (Cmin)
Will be estimated using standard non-compartmental methods
Area under the serum concentration-time curve (AUC)
Will be estimated using standard non-compartmental methods

Secondary Outcome Measures

Full Information

First Posted
April 18, 2012
Last Updated
July 13, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01582191
Brief Title
Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer
Official Title
A Phase 1 Trial of Vandetanib (a Multi-Kinase Inhibitor of EGFR, VEGFR, and RET Inhibitor) in Combination With Everolimus (an mTOR Inhibitor) in Advanced Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 14, 2012 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) or highest dose level, and the dose-limiting toxicity (DLT) of vandetanib (a multi-kinase inhibitor of epidermal growth factor receptor [EGFR], vascular endothelial growth factor receptor [VEGFR] and ret proto-oncogene [RET] inhibitor) when used in combination with everolimus (a mammalian target of rapamycin [mTOR] inhibitor) in advanced cancer. II. Preliminary descriptive assessment of the anti-tumor efficacy of the combination. III. Preliminary optional assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response. OUTLINE: This is a dose-escalation study. Patients receive vandetanib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment patients are followed up between 14-28 days at the discretion of the treating physician.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm, Refractory Malignant Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
153 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vandetanib, everolimus)
Arm Type
Experimental
Arm Description
Patients receive vandetanib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Optional correlative studies
Intervention Type
Drug
Intervention Name(s)
Vandetanib
Other Intervention Name(s)
AZD6474, Caprelsa, Zactima, ZD-6474, ZD6474
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Description
Will be defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%. Toxicity will be reported by type, frequency, and severity. Worst toxicity grades per patient will be tabulated for selected adverse events and laboratory measurements.
Time Frame
28 days
Title
Anti-tumor efficacy of the combination in terms of response rate
Description
The response rate will be estimated by dose level and tumor type, along with the exact 95% confidence interval. Efficacy will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria described in the supplement for response. Patients with lymphoma will be measured per the World Health Organization (WHO) criteria.
Time Frame
Up to 14 years
Title
Maximum observed serum concentration (Cmax)
Description
Will be estimated using standard non-compartmental methods
Time Frame
Days 1 and 21 of course 1 and day 1 of course 3
Title
Pharmacodynamic (PD) parameters
Description
PD biomarker concentration will be summarized by time points. The relationship between drug concentrations and PD effects will be explored graphically. Based on review of these graphs, analyses to describe the relationship may also be performed.
Time Frame
Up to 14 years
Title
Observed trough serum concentration (Cmin)
Description
Will be estimated using standard non-compartmental methods
Time Frame
Days 1 and 21 of course 1 and day 1 of course 3
Title
Area under the serum concentration-time curve (AUC)
Description
Will be estimated using standard non-compartmental methods
Time Frame
Days 1 and 21 of course 1 and day 1 of course 3

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months. Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy. Patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; In addition, patients must be at least 3 weeks beyond the last session of radiation therapy. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment. ECOG performance status should be less or equal to 3 Patients must have organ and marrow function defined as: Absolute neutrophil count more or equal to 750/mL; platelets more or equal to 50,000/mL; creatinine less or equal to 3x ULN; total bilirubin less than or equal to 3.0. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence). Exclusion Criteria: Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support. Pregnant or lactating women. History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation. History of hypersensitivity to sirolimus, temsirolimus, everolimus. History of hypersensitivity to any component of the formulation. Patients unwilling or unable to sign informed consent document. Presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. History (within the last 3 months) or presence of stroke/cerebrovascular accident. Congenital long QT syndrome. QTcF interval greater than 500 ms that is not correctable to less than 500ms such as with cessation of a causative medication, etc. History of myocardial infarction within 6 months with a residual arrhythmia that in the opinion of the Investigator, increases the risk of ventricular arrhythmia. Presence of a symptomatic bradyarrhthmia or uncompensated heart failure.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarina Piha-Paul, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25982012
Citation
Subbiah V, Berry J, Roxas M, Guha-Thakurta N, Subbiah IM, Ali SM, McMahon C, Miller V, Cascone T, Pai S, Tang Z, Heymach JV. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases. Lung Cancer. 2015 Jul;89(1):76-9. doi: 10.1016/j.lungcan.2015.04.004. Epub 2015 Apr 22.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

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Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

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